Blau syndrome

Overview

Blau syndrome is a rare, inherited autoinflammatory disorder characterized by a triad of granulomatous arthritis, uveitis (eye inflammation), and a skin rash. It typically begins in early childhood, often before the age of 5. The condition was first described by Dr. Edward Blau in 1985. Blau syndrome results in chronic inflammation that affects various organs and tissues, and its clinical course can be progressive if not properly managed. It shares similarities with early-onset sarcoidosis, and the two conditions are now considered to be part of the same disease spectrum.

Causes

Blau syndrome is caused by mutations in the NOD2 (also known as CARD15) gene. This gene plays a role in the immune system by regulating the body's inflammatory response. Mutations lead to uncontrolled inflammation and granuloma formation (clusters of immune cells). The condition is inherited in an autosomal dominant pattern, meaning a child only needs one copy of the mutated gene from either parent to develop the disorder. However, some cases may result from new (de novo) mutations with no family history.

Symptoms

Blau syndrome commonly presents in early childhood and typically includes the following symptoms:

• Arthritis – often symmetrical and involving multiple joints, particularly the wrists, ankles, and knees. It may lead to joint stiffness, swelling, and contractures over time.

• Uveitis – chronic, bilateral eye inflammation that can cause redness, pain, light sensitivity, and vision problems. If untreated, it can lead to complications such as cataracts, glaucoma, or even blindness.

• Skin rash – usually appears as a red or brownish, scaly, or bumpy rash, often seen on the trunk and limbs during infancy or early childhood.

Additional features that may occur in some patients include fever, lymphadenopathy (swollen lymph nodes), hepatosplenomegaly, and inflammation in other organs such as the liver, kidneys, or blood vessels.

Diagnosis

Diagnosing Blau syndrome can be challenging due to its overlap with other inflammatory or autoimmune diseases. The diagnostic process involves:

• Clinical evaluation – based on the presence of the classic triad: arthritis, uveitis, and skin rash

• Family history – assessment for similar symptoms in relatives

• Skin or synovial biopsy – revealing non-caseating granulomas, which support the diagnosis

• Genetic testing – confirming mutations in the NOD2 gene, which definitively establishes the diagnosis

• Eye examination – by an ophthalmologist to evaluate uveitis and its severity

Treatment

There is no cure for Blau syndrome, but treatment focuses on controlling inflammation and preventing organ damage. Management typically involves:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – for joint pain and inflammation

• Corticosteroids – used to reduce inflammation in joints, eyes, and skin

• Immunosuppressive agents – such as methotrexate, azathioprine, or mycophenolate mofetil for more severe or steroid-resistant cases

• Biologic therapies – anti-TNF agents (like adalimumab or infliximab) or IL-1 and IL-6 inhibitors have shown promise in controlling symptoms

• Ophthalmologic treatment – including corticosteroid eye drops and systemic therapy to manage uveitis

• Physical therapy – to preserve joint mobility and function

Prognosis

The prognosis of Blau syndrome varies depending on the severity and timing of treatment. With early and aggressive management, many patients can maintain a good quality of life. However, untreated or poorly controlled inflammation—particularly uveitis—can lead to serious complications like joint deformities and permanent vision loss. Lifelong monitoring and a multidisciplinary care approach involving rheumatologists, ophthalmologists, and genetic counselors are essential for optimal outcomes.